1. Field of the Invention
An increasingly important process for delivering a functional material to a particular locus involves the use of microcapsules. As the term is used in the art, a microcapsule contains a functional material encapsulated in a membrane.
An important application of microcapsules is in the medical arts. In this field of application, a functional drug is encapsulated in a membrane that is semipermeable to the drug. When the drug is administered to the host, the drug is transported across the semipermeable membrane to release the drug to the host.
Especially with certain polymers, such as biodegradeable polymers, a need exists for improved methods of forming microcapsules, especially true microcapsules encapsulating a liquid functional core, particularly where the liquid functional core is an aqueous liquid or a suspension in aqueous liquid. With lactides, glycolides and their copolymers, avoiding agglomeration due to their tackiness has been a major obstacle until this invention.
2. Description of the Prior Art
Encapsulation processes including microencapsulation have been known for many years. Methods of microencapsulation include: phase separation techniques, based on, for example, chilling or solvent evaporation; interfacial polycondensation, spray drying, and spraying in a fluidized bed.
Phase Separation Encapsulation is typically a process for preparing Microcapsules in which the core material to be encapsulated is dispersed, customarily by stirring, in a solvent solution of a polymer. While continuing stirring to keep the core material uniformly dispersed throughout the polymer solution, a nonsolvent liquid is added to the polymer solution to change the polymer solubility in the medium and cause a phase separation of the dissolved polymer. Depending upon the specific polymer/solvent system, the polymer either precipitates from the solution or two immiscible liquid phases are produced, one of which is rich in polymer and polymer solvent and poor in nonsolvent, and the second of which is rich in nonsolvent and poor in solvent and polymer. Under certain conditions, the polymer rich phase will migrate to the interface between the dispersed droplets/particles and the continuous phase (non-solvent rich dispersing medium). The suspended particles of the core material are encapsulated with the polymer and are subsequently hardened and recovered from the solvent/nonsolvent medium.
Phase separation relying on solvent evaporation typically involves dissolving the wall material in a water immiscible organic solvent. The core material is also added to the organic solvent forming a suspension or solution of wall material, core material and solvent.
This suspension or solution is then added to a beaker of water with vigorous stirring forming an emulsion. Evaporation of the organic solvent under vacuum causes the precipitation and formation of solid microcapsules.
In almost all of the prior art processes involving lactides, glycolides and their copolymers, the capsules formed are not true microcapsules in the sense of being reservoir type devices. In other words typically the microcapsules which are formed comprise a wall material encapsulating a solid core, the solid core typically consisting of solid drug particles homogeneously dispersed in a solid polymer matrix. Thus the prior art product is closer to a microsphere than a true capsule.
A need exists in the art for reliable methods for forming true microcapsules from lactides, glycolides, and their copolymers, i.e., reservoir type devices, encapsulating a liquid core particularly an aqueous liquid core, oil in water emulsion or suspension.